Synthesis, experimental and molecular dynamics simulation of the ESI-CID spectrum of the nerve agent Novichok analog O-2-methoxyethyl N- [bis(dimethylamino)methylidene]-P-methylphosphonamidate

The comprehensive and accurate analysis of mass spectral data is critical for the unequivocal identification of environmental samples containing compounds short-listed by the Chemical Weapons Convention (CWC). In particular, experiments with nerve agents are limited by the high risks involved in their handling. Therefore, the possibility of studying fragmentation pathways by a theoretical approach is especially welcome. In this work, for the first time, O-2-methoxyethyl N- [bis(dimethylamino)methylidene]-P-methylphosphonamidate, an analog of the Novichok nerve agent A-242, was synthesized employing a one-pot microscale synthesis. Electron ionization (EI) and electrospray ionization (ESI) mass spectra (MS) were measured to provide data for CWC verification purposes. Considering that ESI-MS/MS is a powerful method for analyzing non-volatile, highly polar, and very water-soluble compounds, such as degradation products of nerve agents, we extensively investigated for the first time the ESI-(collision-induced dissociation) CID fragmentation pathways of the selected molecule. For this purpose, molecular dynamics simulations using the Quantum Chemical Mass Spectrometry (QCxMS) method employing the semiempirical electronic structure method GFN2-xTB were compared with Triple Quadrupole electrospray ionization (ESI) experimental spectra in positive ion mode. The base peak of the EI spectrum for this molecule was found to be m/z 151, which strongly suggests a McLafferty +1 (ML+1) rearrangement involving the 2-methoxyethyl moiety. The formation of ion the m/z 106 in the ESI-CID spectrum, according to the simulations, results from the rearrangement involving a transfer of one dimethylamino group to the phosphorus atom, a mechanism that would be difficult to identify without employing theoretical methods.